Tissue Microarray Applications in Drug Discovery for Pancreatic Cancer



The rising incidence of pancreatic cancer combined with limited responses to chemotherapy highlights the need for improved molecular characterization in this highly lethal cancer. The discovery and validation of novel biomarkers are urgently needed to improve early detection and thereby improve survival outcomes. The introduction and widespread application of tissue microarrays (TMAs) over the past decade provide a valuable tool for validation of abundance and cellular localization of expressed proteins and RNA transcript levels contextually within the complex tissue morphology of pancreatic cancer. The TMA format offers a standardized platform to optimize and validate newly identified biomarkers and drug targets in pancreatic cancer research to patient tumor samples to provide critical links in advancing cancer research findings to the clinical setting.


Pancreatic Cancer Tissue Core FFPE Tissue Formalin Fixation National Human Genome Research Institute 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abbott RT, Tripp S, Perkins SL et al (2003) Analysis of the PI-3-Kinase-PTEN-AKT pathway in human lymphoma and leukemia using a cell line microarray. Mod Pathol 16:607–612CrossRefPubMedGoogle Scholar
  2. Andersen CL, Hostetter G, Grigoryan A et al (2001) Improved protocol for fluorescence in situ hybridization on tissue microarrays. Cytometry 45:83–86CrossRefPubMedGoogle Scholar
  3. Balagurunathan Y, Morse DL, Hostetter G et al (2008) Gene expression profiling-based identification of cell-surface targets for developing multimeric ligands in pancreatic cancer. Mol Cancer Ther 7:3071–3080CrossRefPubMedGoogle Scholar
  4. Battifora H (1986) The multitumor (sausage) block: novel method for immunohistochemistry antibody testing. Lab Invest 55:244–248PubMedGoogle Scholar
  5. Bubendorf L, Kononen J, Koivisto P et al (1999) Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res 59:803–806PubMedGoogle Scholar
  6. Cao D, Zhang Q, Wu L et al (2007) Prognostic significance of maspin in pancreatic ductal adenocarcinoma: tissue microarray analysis of 223 surgically resected cases. Mod Pathol 20:570–578CrossRefPubMedGoogle Scholar
  7. Charpin C, Dales JP, Garcia S et al (2004) Tumor neoangiogenesis by CD31 and CD105 expression evaluation in breast carcinoma tissue microarrays. Clin Cancer Res 10:5815–5819CrossRefPubMedGoogle Scholar
  8. Chiesa-Vottero AG, Rybicki LA, Prayson RA (2003) Comparison of proliferation indices in glioblastoma multiforme by whole tissue section vs. tissue microarray. Am J Clin Pathol 120:902–908CrossRefPubMedGoogle Scholar
  9. Chin SF, Daigo Y, Huang HE et al (2003) A simple and reliable pretreatment protocol facilitates fluorescent in situ hybridisation on tissue microarrays of paraffin wax embedded tumor samples. Mol Pathol 56:275–279CrossRefPubMedGoogle Scholar
  10. Collins FS, McKusick VA (2001) Implications of the Human Genome Project for medical science. JAMA 285:540–544CrossRefPubMedGoogle Scholar
  11. De Marzo AM, Fedor HH, Gage WR et al (2002) Inadequate formalin fixation decreases reliability of p27 immunohistochemical staining: probing optimal fixation time using high-density tissue microarrays. Hum Pathol 33:756–760CrossRefPubMedGoogle Scholar
  12. DeRisi J, Penland L, Brown PO et al (1996) Use of a cDNA microarray to analyze gene expression patterns in human cancer. Nat Genet 14:457–460CrossRefPubMedGoogle Scholar
  13. DiVito KA, Charette LA, Rimm DL et al (2004) Long-term preservation of antigenicity on tissue microarrays. Lab Invest 84:1071–1078CrossRefPubMedGoogle Scholar
  14. Duggan DJ, Bittner M, Chen Y et al (1999) Expression profiling using cDNA microarrays. Nat Genet 21(1 Suppl):10–14CrossRefPubMedGoogle Scholar
  15. Fejzo MS, Slamon DJ (2001) Frozen tumor tissue microarray technology for analysis of tumor RNA, DNA, and proteins. Am J Pathol 159:1645–1650Google Scholar
  16. Fergenbaum JH, Garcia-Closas M, Hewitt SM et al (2004) Loss of antigenicity in stored sections of breast cancer tissue microarrays. Cancer Epidemiol Biomarkers Prev 13:667–672PubMedGoogle Scholar
  17. Frantz GD, Pham TQ, Peale FV et al (2001) Detection of novel gene expression in paraffin-embedded tissues by isotopic in situ hybridization in tissue microarrays. J Pathol 195:87–96CrossRefPubMedGoogle Scholar
  18. Garcia JF, Camacho FI, Morente M et al (2003) Spanish Hodgkin Lymphoma Study Group. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood 101:681–689CrossRefPubMedGoogle Scholar
  19. Gulmann C, Butler D, Kay E Grace et al (2003) Biopsy of a biopsy: validation of immunoprofiling in gastric cancer biopsy tissue microarrays. Histopathology 42:70–76CrossRefPubMedGoogle Scholar
  20. Hacia JG, Edgemon K, Fang N et al (2000) Oligonucleotide microarray based detection of repetitive sequence changes. Hum Mutat 16:354–363CrossRefPubMedGoogle Scholar
  21. Han C, Lee M, Tzeng S et al (2008) Nuclear receptor interaction protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization. J Exp Clin Cancer Res 27:25CrossRefPubMedGoogle Scholar
  22. Hardisson D, Moreno-Bueno G, Sanchez L et al (2003) Tissue microarray immunohistochemical expression analysis of mismatch repair (hMLH1 and hMSH2 genes) in endometrial carcinoma and atypical endometrial hyperplasia: relationship with microsatellite instability.Mod Pathol 16:1148–1158CrossRefPubMedGoogle Scholar
  23. Henshall S (2003) Tissue microarrays. J Mammary Gland Biol Neoplasia 8:347–358CrossRefPubMedGoogle Scholar
  24. Hoos A, Cordon-Cardo C (2001) Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations. Lab Invest 81(10):1331–1338PubMedGoogle Scholar
  25. Hoos A, Urist MJ, Stojadinovic A et al (2001) Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors. Am J Pathol 158:1245–1251PubMedGoogle Scholar
  26. Hsieh HL, Schafer BW, Sasaki N et al (2003) Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays. Biochem Biophys Res Commun 307:375–381CrossRefPubMedGoogle Scholar
  27. Hsu FD, Neilson TO, Alkushi A et al (2002) Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochemistry. Mod Pathol 15:1374–1380CrossRefPubMedGoogle Scholar
  28. Hu YC, Komorowski RA, Graewin S et al (2003) Thymidylatesynthase expression predicts the response to 5-fluorouracil-based adjuvant therapy in pancreatic cancer. Clin Cancer Res 9:4165–4171PubMedGoogle Scholar
  29. Khorana AA, Ahrendt SA, Ryan CK et al (2007) Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 13:2870–2875CrossRefPubMedGoogle Scholar
  30. Kononen J, Bubendorf L, Kallioniemi A et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847CrossRefPubMedGoogle Scholar
  31. Kononen J, Hostetter G, Sauter G et al (2002) Construction of tissue microarrays. David Bowtell and Joe Sambrook (Eds.) In: DNA Microarrays: A Molecular Cloning Manual, Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  32. Li H, Sun Y, Kong QY et al (2003) Combination of nucleic acid and protein isolation with tissue array construction: using defined histologic regions in single frozen tissue blocks for multiple research purposes. Int J Mol Med 12:299–304PubMedGoogle Scholar
  33. Maitra A, Adsay NV, Argani P et al (2003) Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarray. Mod Pathol 16:902–912CrossRefPubMedGoogle Scholar
  34. Merseburger AS, Kuczyk MA, Serth J et al (2003) Limitations of tissue microarrays in the evaluation of focal alterations of bcl-2 and p53 in whole mount derived prostate tissues. Oncol Rep 10:223–228PubMedGoogle Scholar
  35. Mobasheri A, Airley R, Foster CS et al (2004) Post-genomic applications of tissue microarrays: basic research, prognostic oncology, clinical genomics and drug discovery. Histol Histopathol 19:325–335PubMedGoogle Scholar
  36. Moskaluk CA, Stoler MH (2002) Agarose mold embedding of cultured cells for tissue microarrays. Diagn Mol Pathol 11:234–238CrossRefPubMedGoogle Scholar
  37. Mousses S, Bubendorf L, Wagner U et al (2002) Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays. Cancer Res 62:1256–1260PubMedGoogle Scholar
  38. Mucci N, Akdas G, Manley S et al (2000) Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. Hum Pathol 31:406–414CrossRefPubMedGoogle Scholar
  39. Nishizuka S, Chen ST, Gwadry FG et al (2003) Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. Cancer Res 63:5243–5250PubMedGoogle Scholar
  40. Nocito A, Bubendorf L, Tinner ME et al (2001) Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol 194:349–357CrossRefPubMedGoogle Scholar
  41. O’Leary TJ (2001) Standardization in immunohistochemistry. Appl Immunohistochem Mol Morphol 9:3–8CrossRefPubMedGoogle Scholar
  42. Parker RL, Gilks CB et al (2002) Assessment of interlaboratory variation in immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol 117:723–728CrossRefPubMedGoogle Scholar
  43. Rimm D, Camp R, Charette L et al (2001) Tissue microarray: a new technology of amplification of tissue resources. Cancer J 7:24–31PubMedGoogle Scholar
  44. Rubin MA, Dunn R et al (2002) Tissue microarray sampling strategy for prostate cancer biomarkers analysis. Am J Surg Pathol 26:312–319CrossRefPubMedGoogle Scholar
  45. Sauter G, Simon R, Hillan K (2003) Tissue microarrays in drug discovery. Nat Rev Drug Discov 2:962–972CrossRefPubMedGoogle Scholar
  46. Saxby AJ, Nielsen A, Scarlett CJ et al (2005) Assessment of Her-2 status in pancreatic adenocarcinoma. Am J Surg Pathol 29:1125–1134CrossRefPubMedGoogle Scholar
  47. Schraml P, Kononen J, Bubendorf L et al (1999) Tissue microarrays for gene amplification surveys in many different tumor types. Clin Cancer Res 5:1966–1975PubMedGoogle Scholar
  48. Simon R, Mirlacher M, Sauter G (2004) Tissue microarrays. Biotechniques 36:98–105PubMedGoogle Scholar
  49. Skacel M, Skilton B, Pettay JD et al (2002) Tissue microarrays: a powerful tool for high-throughput analysis of clinical specimens: a review of the method with validation data. Appl Immunohistochem Mol Morphol 10:1–6CrossRefPubMedGoogle Scholar
  50. Sompuram SR, Kodela V, Zhang K et al (2002) A novel quality control slide for quantitative immunohistochemistry testing. J Histochem Cytochem 50:1425–1434PubMedGoogle Scholar
  51. Srivastava M, Bubendorf L, Srikantan V et al (2001) ANX7, a candidate tumor suppressor gene for prostate cancer. Proc Natl Acad Sci U S A 98:4575–4580CrossRefPubMedGoogle Scholar
  52. Sugita M, Geraci M, Gao B et al (2002) Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res 62:3971–3979PubMedGoogle Scholar
  53. Swierczynski SL, Maitra A, Nirban AS et al (2004) Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays. Hum Pathol 35:357–366CrossRefPubMedGoogle Scholar
  54. Warford A, Howat W, McCafferty J (2004) Expression profiling by high-throughput immunohistochemistry. J Immunol Methods 290:81–92CrossRefPubMedGoogle Scholar
  55. Welsh JB, Sapinoso LM, Kern SG et al (2003) Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum. Proc Natl Acad Sci U S A 100:3410–3415CrossRefPubMedGoogle Scholar
  56. Wolfsberg TG, Wetterstrand KA, Guyer MS et al (2002) A user's guide to the human genome. Nat Genet 32(Suppl):1–79PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Integrated Cancer Genomics DivisionTranslational Genomics Research InstitutePhoenixUSA

Personalised recommendations